Knockdown of cortical transthyretin expression around implanted neural prosthetic devices using intraventricular siRNA injection in the brain.

Neural prosthetic devices are showing increasing clinical use for the treatment of a variety of neurological disorders. However the functions on these devices are often limited due to an inability to effectively and chronically interface with neural tissue. The insertion of devices has been shown to result in significant cellular and vascular trauma surrounding the insertion site.

Optical monitoring of neural networks evoked by focal electrical stimulation on microelectrode arrays using FM dyes.

Patch-clamping or microelectrode arrays (MEA) are conventional methods to monitor the electrical activity in biological neural networks in vitro. Despite the effectiveness of these techniques, there are disadvantages including the limited number of electrodes and the predetermined location of electrodes in MEAs. In particular, these drawbacks raise a difficulty in monitoring a number of neurons outnumbering the electrodes.

Release of nerve growth factor from HEMA hydrogel-coated substrates and its effect on the differentiation of neural cells.

Local pharmacological intervention may be needed to ensure the long-term performance of neural prosthetic devices because of insertion-related neuron loss and reactive cell responses that form compact sheaths, leading to decreased device performance. We propose that local delivery of neurotrophins would enhance neuron survival and promote neuron sprouting toward device electrodes, thus providing improved electrode-neuron communication and device performance for recording and stimulating CNS activity. In this study, three different types of poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels were developed and assessed for storage capacity and release rates of the neurotrophin, nerve growth factor (NGF).

Modulation of cultured neural networks using neurotrophin release from hydrogel-coated microelectrode arrays.

Polyacrylamide and poly(ethylene glycol) diacrylate hydrogels were synthesized and characterized for use as drug release and substrates for neuron cell culture. Protein release kinetics was determined by incorporating bovine serum albumin (BSA) into hydrogels during polymerization. To determine if hydrogel incorporation and release affect bioactivity, alkaline phosphatase was incorporated into hydrogels and a released enzyme activity determined using the fluorescence-based ELF-97 assay.

Improved detection of branching points in algorithms for automated neuron tracing from 3D confocal images.

Automated tracing of neuronal processes from 3D confocal microscopy images is essential for quantitative neuroanatomy and neuronal assays. Two basic approaches are described in the literature-one based on skeletonization and another based on sequential tracing along neuronal processes. This article presents algorithms for improving the rate of detection, and the accuracy of estimating the location and process angles at branching points for the latter class of algorithms.

Directed cell growth on protein-functionalized hydrogel surfaces.

Biochemical surface modification has been used to direct cell attachment and growth on a biocompatible gel surface. Acrylamide-based hydrogels were photo-polymerized in the presence of an acroyl-streptavidin monomer to create planar, functionalized surfaces capable of binding biotin-labelled proteins. Soft protein lithography (microcontact printing) of proteins was used to transfer the biotinylated extracellular matrix proteins, fibronectin and laminin, and the laminin peptide biotin-IKVAV, onto modified surfaces.

Synaptic connectivity of a low density patterned neuronal network produced on the poly-L-lysine stamped microelectrode array.

Rectangular networks of rat hippocampal neurons have been produced on microelectrode arrays (MEAs). The crossing points of networks were located at the recording electrode sites by aligned microcontact printing (μCP) technique. Polydimethysiloxane (PDMS) stamp was fabricated to print fine poly-L-lysine (PLL) patterns of 2 -width lines for neurites and 20 -diameter circles for cell bodies.

Functionalized hydrogel surfaces for the patterning of multiple biomolecules.

Patterning of multiple proteins and enzymes onto biocompatible surfaces can provide multiple signals to control cell attachment and growth. Acrylamide-based hydrogels were photo-polymerized in the presence of streptavidin-acrylamide, resulting in planar gel surfaces functionalized with the streptavidin protein. This surface was capable of binding biotin-labeled biomolecules.

Low-density neuronal networks cultured using patterned poly-l-lysine on microelectrode arrays.

Synaptic activity recorded from low-density networks of cultured rat hippocampal neurons was monitored using microelectrode arrays (MEAs). Neuronal networks were patterned with poly-l-lysine (PLL) using microcontact printing (microCP). Polydimethysiloxane (PDMS) stamps were fabricated with relief structures resulting in patterns of 2 microm-wide lines for directing process growth and 20 microm-diameter circles for cell soma attachment.

Automatic selection of parameters for vessel/neurite segmentation algorithms.

An automated method is presented for selecting optimal parameter settings for vessel/neurite segmentation algorithms using the minimum description length principle and a recursive random search algorithm. It trades off a probabilistic measure of image-content coverage against its conciseness. It enables nonexpert users to select parameter settings objectively, without knowledge of underlying algorithms, broadening the applicability of the segmentation algorithm, and delivering higher morphometric accuracy.

Extracellular recordings from patterned neuronal networks using planar microelectrode arrays.

Neuronal cell networks have been reconstructed on planar microelectrode arrays (MEAs) from dissociated hippocampal pyramidal neurons. Microcontact printing (microCP) and a photoresist-liftoff method were used to selectively localize poly-L-lysine (PLL) on the surface of MEAs. Haptotaxis led to the organization of the neurons into networks localized adjacent to microelectrodes.

Median-based robust algorithms for tracing neurons from noisy confocal microscope images.

This paper presents a method to exploit rank statistics to improve fully automatic tracing of neurons from noisy digital confocal microscope images. Previously proposed exploratory tracing (vectorization) algorithms work by recursively following the neuronal topology, guided by responses of multiple directional correlation kernels. These algorithms were found to fail when the data was of lower quality (noisier, less contrast, weak signal, or more discontinuous structures).